Ecocyc database

ECOCYC DATABASE
Presented by:
Shiv kumar
M.Sc (Microbial Biotechnology)

Introduction:
 EcoCyc word comes from E.coli (Eco) and Encyclopaedia (cyc).
 The encyclopedia of Escherichia coli K-12 genes and metabolism
(EcoCyc) is a database that combines information about the genome
and the intermediary metabolism of E.coli .
 It describes the known genes of E.coli , the enzymes encoded by
these genes, the reactions catalyzed by each enzyme and the
organization of these reactions into metabolic pathways.
 It is a freely accessible, comprehensive database that collects and
summarizes experimental data for Escherichia coli K-12 at
EcoCyc.org .
 It has graphical user interface (GUI) which allows query, exploration
and visualization of the EcoCyc database. EcoCyc spans the space
from sequence to function to allow investigatation of an unusually
broad range of questions .
 It is Curation based database in which Curation is the process of
manually refining and updating a bioinformatics database. The EcoCyc
project uses a literature-based Curation approach in which database
updates are based on evidence in the experimental literature.

Cont…
 The EcoCyc system consists of a knowledge base (KB) that describes
the genes and intermediary metabolism of E. coli, and a graphical user
interface for accessing that knowledge.
 EcoCyc is joint work between our group at SRI International, and a
group at the Marine Biological Laboratory (MBL) led by Monica
Riley.
 Taken together, the knowledge base and the graphical user interface
(GUI) constitute an electronic encyclopedia that allows scientists to
visualize and explore an integrated collection of genomic and
biochemical information.
 By integrating genomic data with comprehensive knowledge of the
metabolic functions of gene products, we greatly increase the value of
the genomic data and the types of analyses that can be applied to it.

Why it is designed?
It is designed for several different modes of interactive use via both the
EcoCyc.org web site and in conjunction with the downloadable
Pathway Tools software:
 It is a Visualization tools in which genome browser, metabolic
map display, and regulatory network diagram and aid in the
comprehension of these complex data found.
 EcoCyc facilitates analysis of high-throughput data such as gene-
expression and metabolomics data via tools for enrichment
analysis, and for visualizing omics data on a metabolic map
diagram, complete genome diagram, or regulatory network
diagram.
 The EcoCyc metabolic flux model can predict growth or no-growth
of wildtype and knock-out E. coli strains under different nutrient
conditions.

Problems that might be solved by using
EcoCyc:
 Genomic investigations
Coupled with sequence databases EcoCyc could be used to perform
function-based retrieval of DNA or protein sequences, such as to prepare
data sets for studies of protein structure-function relationships. Microbial
geneticists who work with bacteria other than E.coli will find EcoCyc useful
as a point of reference for gene functions, as well as for similarities and
differences in gene-product relationships.
 Studies of the metabolism
Scientists who study the evolution of the metabolism could use EcoCyc to
search out examples of duplication and divergence of enzymes and
pathways. Systematic computational studies of pathway evolution can
compare related pathways from different organisms. EcoCyc provides a
foundation for automatically generating simulations of the metabolism,
although it lacks the kinetics data needed by most simulation techniques.
 Pathway design for biotechnology
Biotechnologists seek to design novel biochemical pathways that produce
useful chemical products (such as pharmaceuticals) or that catabolize
unwanted chemicals such as toxins. EcoCyc provides the wiring diagram
of E.coli K-12, which approximates the starting point for engineering.
EcoCyc also describes the potential engineering variations that can result
from importing E.coli enzymes into other organisms.

 The Ecocyc Graphical User Interface
 The EcoCyc GUI provides graphical tools for visualizing and navigating
through an integrated collection of metabolic and genomic information
(its retrieval capabilities are described in Retrieval operations). For
each type of biological object in the EcoCyc database the GUI
provides a corresponding visualization tool.
 These tools dynamically query the underlying database to produce
display windows. Other displays are provided for genes, enzymes,
compounds and for browsing genomic maps.
 All the display algorithms are parameterized to allow the user to select
the visual presentation of an object that is most informative.
 For example, the algorithms that produce automatic layouts of
metabolic pathways can suppress the display of enzyme names or
side compound names. They can also draw chemical structures for the
compounds within a pathway.

Circular map browser for the E.coli chromosome.The bar at right shows a magnification
of the region between 51 and 55 centisomes. Bars over gene names indicate counter
clockwise transcription.

 The Ecocyc Data
 The EcoCyc data are stored within a frame knowledge representation system (FRS),
which is similar to an object-oriented database.
 FRSs use an object-oriented data model and have several advantages over relational
database management systems . FRSs organize information within classes,
collections of objects that share similar properties and attributes.
 Each EcoCyc frame contains slots describing attributes or properties of the biological
object that the frame represents or encoding a relationship between that object and
other objects. For example, the slots of a polypeptide frame encode the molecular
weight of the polypeptide, the gene that encodes it and its cellular location.

1. Genes
 Most genes whose product is an enzyme to an EcoCyc object that
represents the polypeptide and added a textual description of the
product for genes whose product is not an EcoCyc object.
 Data taken from EcoCyc v15.0:

2. Compounds
 This discussion focuses on small metabolites, which are instances of the class
Compounds.
 The data on compounds involved in the intermediary metabolism of E.coli , but
data on some other compounds are also present, for example metabolites from
other organisms.
 Among the properties encoded for compounds are synonyms, molecular weight,
empirical formula, lists of bonds and atoms that encode chemical structures and
two-dimensional display coordinates for each atom that permit the drawing of
compound structures. EcoCyc contains 1830 compounds, of which 964 have
recorded two-dimensional structures.
3. Reactions
 The initial set of biochemical reactions in EcoCyc were derived from the ENZYME
database, Because enzyme nomenclature concerns enzymes from all species,
many of the reactions in the ENZYME database, and therefore in EcoCyc, do not
actually occur in E.coli .
 Reaction frames contain information such as lists of reactants and products for
the reaction equation, the EC number of the reaction and AG 0 for the reaction in
the direction it is written. Reaction objects are linked to the pathway(s) that
contains them and to the enzyme(s) that catalyzes them. EcoCyc contains 2901
reactions organized into the 258 classes defined by the enzyme committee. Of
these, 580 reactions are known to occur in E.coli . Only 14 of the reactions have
no EC number.

 Proteins
 Template files organize information as frames (such as enzymes and
pathways) with labeled slots (attributes). The template files also permit
association of chosen literature citations with the appropriate data. In each
frame there are multiple opportunities for liberal comment, to describe the
metabolic functions and the unique complex properties of the reaction or the
enzyme.
 Among the topics covered by comments in EcoCyc are reaction mechanisms,
subreactions of complex reactions, interactions of subunits of complex
enzymes, formation of complexes with other proteins, breadth of substrate
specificity, mode of action of inhibitors and activators, place and function of
reactions in metabolic pathways, other reactions catalyzed by the protein and
the relationship of the protein to other proteins catalyzing the same reaction.
 Karp has developed a computer program that parses the template files to
extract their constituent data items and then inserts those data items into the
EcoCyc database. The parser program also performs consistency checks on
the data and allows interactive correction of problems that are found.
Consistency checkers can correct minor typographical errors and verify, for
example, that the entry in a field that is supposed to contain a gene does in fact
refer to a gene in the database. These tools have proven vital in detecting
errors throughout the database.

In the EcoCyc schema all enzyme objects are instances of the
class Proteins, which is partitioned into two subclasses:
 Protein Complexes and Polypeptides.
 These two classes have a number of common properties, such as molecular
weight, pI, cellular location and a relationship to one or more catalyzed
reactions. They differ in that Protein Complexes have slots that link them to
their subunits, whereas Polypeptides have a slot that identifies their gene.
 We also record known sequence similarity relationships among a set of
isozymes and we provide links to the SWISS-PROT and PDB entries for a
polypeptide.
 Proteins are listed as a subclass of chemical compounds, since in some cases
enzymes themselves are substrates in a reaction (such as phosphorylation
reactions).
 The database contains 468 polypeptides and 238 protein complexes that
comprise a total of 306 enzymes (i.e. 306 of the polypeptides and protein
complexes have defined catalytic activities).

Enzymatic reactions
 We define a high fidelity representation as a formal conceptualization (i.e. a portion of a
schema) that allows a database to accurately capture subtleties of biology. For example, a
number of other metabolic databases do not explicitly distinguish enzymes from reactions
nor polypeptides from protein complexes.
 But the properties of a reaction (such as its Δ G 0 and its substrates) are independent of the
enzyme(s) that catalyzes it and the properties of an enzyme (such as its molecular weight
and amino acid sequence) are independent of the reactions it catalyzes.
 The relationships between enzymes and reactions are many to many, since one enzyme
can catalyze many reactions and one reaction can be catalyzed by more than one enzyme.
This distinction has led to interesting and perhaps counterintuitive observations. EC
numbers are actually a property of reactions, rather than of enzymes, i.e. there is a one to
one correspondence between reactions and EC numbers, but not between enzymes and
EC numbers. An enzyme that catalyzes two reactions will have two EC numbers and two
enzymes that catalyze the same reaction have the same EC number.
 A further distinction is required because some properties of an enzyme are meaningful only
in the context of a particular reaction that the enzyme catalyzes. Properties such as
activators, inhibitors and cofactors pertain to the pairing of an enzyme and a reaction,
because a single enzyme that catalyzes two reactions may be sensitive to different
inhibitors for each reaction and we wish to capture this complex relationship.

Design Requirements
The EcoCyc GUI was created to facilitate the latter types of consultation
— to provide biologists with powerful and intuitive tools for exploring
and comprehending the elements of a complex information space. The
design of the EcoCyc GUI was mainly influenced by the scientific tasks
for which the information will be used, and the properties of the
information itself.
 Molecular biologists and biotechnologists designing a cloning project
will have instant access to the best current information on map
locations, identities of linked genes and their functions, lists of
available clones, and locations of pertinent restriction sites.
 Molecular evolutionists could use such DBs to search out examples of
duplication and divergence, and ancestral relationships among genes,
enzymes, and pathways.
 The metabolic pathways present in an organism can be predicted from
the DNA sequence of the organism plus its nutritional requirements,
given sufficient background knowledge of metabolism.
 A scientist who has found sequence similarities between a gene of
interest and one or more E. coli genes could use EcoCyc to obtain
descriptions of the functions of the E. coli genes. EcoCyc contains
more detailed descriptions of function than do the sequence DBs.

Cont…
 Biotechnologists seek to design novel biochemical pathways that
produce useful chemical products (such as flavor enhancers in food,
amino acids and vitamins, or pharmaceuticals), or that catabolize
unwanted chemicals such as toxins. Metabolic DBs can provide
information about enzymes from other organisms with novel substrate
specificities, kinetics, or regulatory characteristics, that can modify a
metabolic network.
 Scientists who study the metabolism itself will be able to pose novel
questions of broader scope than previously possible. Systematic
computational studies of pathway evolution can compare many related
pathways from different organisms. Those who employ numerical
simulation techniques will benefit from collections of enzyme-kinetics
data. •
 The comprehensive characterizations of enzyme function in metabolic
DBs will make possible systematic computational studies of protein
structure–function relationships.

SoftwareArchitecture
The EcoCyc software architecture is shown in Figure . The
major components of the system are
 A frame knowledge representation system called HyperTHEO that
manages the EcoCyc KB.
 A graphical KB editor and browser called the GKB Editor.
 The EcoCyc GUI. All communication between the EcoCyc GUI and
HyperTHEO flows through a well-defined KB-access library called the
Generic-Frame Protocol (Karp et al., 1995), making the EcoCyc GUI a
modular component that is in principle separable from HyperTHEO.
 A system for manipulating and displaying graphs, called Grasper-CL.
Another reason for the quick development of EcoCyc is the fact that its
pathway displays were implemented using the high-level graph display
and layout capabilities within Grasper-CL.
 CWEST is a tool for retrofitting CLIM applications to run through the
WWW. CWEST dynamically translates CLIM graphics to a combination
of HTML and GIF images for transmission via the WWW. CWEST
allows the EcoCyc GUI to operate over the WWW in a manner that is
very similar to its X-windows operation.

Figure :The architecture of the EcoCyc system

Ecocyc database

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